CN1470247A - Bone repairing material - Google Patents
Bone repairing material Download PDFInfo
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- CN1470247A CN1470247A CNA021256144A CN02125614A CN1470247A CN 1470247 A CN1470247 A CN 1470247A CN A021256144 A CNA021256144 A CN A021256144A CN 02125614 A CN02125614 A CN 02125614A CN 1470247 A CN1470247 A CN 1470247A
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- bone
- chitin
- chitosan
- renovating material
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- 210000000988 bone and bone Anatomy 0.000 title claims abstract description 55
- 239000000463 material Substances 0.000 title claims abstract description 37
- 229920002101 Chitin Polymers 0.000 claims abstract description 33
- 229920001661 Chitosan Polymers 0.000 claims abstract description 27
- 239000002639 bone cement Substances 0.000 claims abstract description 22
- 238000006467 substitution reaction Methods 0.000 claims description 14
- 230000006196 deacetylation Effects 0.000 claims description 11
- 238000003381 deacetylation reaction Methods 0.000 claims description 11
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 7
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 6
- 230000026731 phosphorylation Effects 0.000 claims description 6
- 238000006366 phosphorylation reaction Methods 0.000 claims description 6
- 230000019635 sulfation Effects 0.000 claims description 6
- 238000005670 sulfation reaction Methods 0.000 claims description 6
- 150000001875 compounds Chemical class 0.000 claims description 3
- 210000001519 tissue Anatomy 0.000 abstract description 6
- 210000000845 cartilage Anatomy 0.000 abstract description 2
- 229920000747 poly(lactic acid) Polymers 0.000 abstract description 2
- 239000004626 polylactic acid Substances 0.000 abstract description 2
- 210000000515 tooth Anatomy 0.000 abstract description 2
- -1 carboxyl-butyl Chemical group 0.000 abstract 1
- 239000001506 calcium phosphate Substances 0.000 description 13
- 229910000389 calcium phosphate Inorganic materials 0.000 description 12
- 241001465754 Metazoa Species 0.000 description 11
- QORWJWZARLRLPR-UHFFFAOYSA-H tricalcium bis(phosphate) Chemical class [Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O QORWJWZARLRLPR-UHFFFAOYSA-H 0.000 description 10
- 230000011164 ossification Effects 0.000 description 9
- 235000011010 calcium phosphates Nutrition 0.000 description 8
- 230000000694 effects Effects 0.000 description 7
- 238000000034 method Methods 0.000 description 7
- 238000002360 preparation method Methods 0.000 description 7
- GBNXLQPMFAUCOI-UHFFFAOYSA-H tetracalcium;oxygen(2-);diphosphate Chemical compound [O-2].[Ca+2].[Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O GBNXLQPMFAUCOI-UHFFFAOYSA-H 0.000 description 7
- VTYYLEPIZMXCLO-UHFFFAOYSA-L Calcium carbonate Chemical compound [Ca+2].[O-]C([O-])=O VTYYLEPIZMXCLO-UHFFFAOYSA-L 0.000 description 6
- 239000013642 negative control Substances 0.000 description 6
- 239000013641 positive control Substances 0.000 description 6
- 239000000243 solution Substances 0.000 description 6
- NBIIXXVUZAFLBC-UHFFFAOYSA-L Phosphate ion(2-) Chemical compound OP([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-L 0.000 description 5
- 230000007547 defect Effects 0.000 description 5
- 206010061218 Inflammation Diseases 0.000 description 4
- 241000283973 Oryctolagus cuniculus Species 0.000 description 4
- 208000027418 Wounds and injury Diseases 0.000 description 4
- 239000012620 biological material Substances 0.000 description 4
- 230000006378 damage Effects 0.000 description 4
- 238000005538 encapsulation Methods 0.000 description 4
- 239000000835 fiber Substances 0.000 description 4
- 238000001727 in vivo Methods 0.000 description 4
- 230000004054 inflammatory process Effects 0.000 description 4
- 208000014674 injury Diseases 0.000 description 4
- 239000000843 powder Substances 0.000 description 4
- 210000004872 soft tissue Anatomy 0.000 description 4
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 4
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 3
- 230000002785 anti-thrombosis Effects 0.000 description 3
- 239000003146 anticoagulant agent Substances 0.000 description 3
- 239000007864 aqueous solution Substances 0.000 description 3
- 230000015572 biosynthetic process Effects 0.000 description 3
- 229910000019 calcium carbonate Inorganic materials 0.000 description 3
- FUFJGUQYACFECW-UHFFFAOYSA-L calcium hydrogenphosphate Chemical compound [Ca+2].OP([O-])([O-])=O FUFJGUQYACFECW-UHFFFAOYSA-L 0.000 description 3
- 239000004568 cement Substances 0.000 description 3
- 235000019700 dicalcium phosphate Nutrition 0.000 description 3
- 229910052588 hydroxylapatite Inorganic materials 0.000 description 3
- 239000007788 liquid Substances 0.000 description 3
- 239000000203 mixture Substances 0.000 description 3
- 230000031990 negative regulation of inflammatory response Effects 0.000 description 3
- XYJRXVWERLGGKC-UHFFFAOYSA-D pentacalcium;hydroxide;triphosphate Chemical compound [OH-].[Ca+2].[Ca+2].[Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O XYJRXVWERLGGKC-UHFFFAOYSA-D 0.000 description 3
- 238000011084 recovery Methods 0.000 description 3
- 108010048734 sclerotin Proteins 0.000 description 3
- 239000007787 solid Substances 0.000 description 3
- IXPNQXFRVYWDDI-UHFFFAOYSA-N 1-methyl-2,4-dioxo-1,3-diazinane-5-carboximidamide Chemical compound CN1CC(C(N)=N)C(=O)NC1=O IXPNQXFRVYWDDI-UHFFFAOYSA-N 0.000 description 2
- 208000010392 Bone Fractures Diseases 0.000 description 2
- HECLRDQVFMWTQS-UHFFFAOYSA-N Dicyclopentadiene Chemical compound C1C2C3CC=CC3C1C=C2 HECLRDQVFMWTQS-UHFFFAOYSA-N 0.000 description 2
- 206010017076 Fracture Diseases 0.000 description 2
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 2
- 208000001132 Osteoporosis Diseases 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
- XLOMVQKBTHCTTD-UHFFFAOYSA-N Zinc monoxide Chemical compound [Zn]=O XLOMVQKBTHCTTD-UHFFFAOYSA-N 0.000 description 2
- 238000010171 animal model Methods 0.000 description 2
- 230000003110 anti-inflammatory effect Effects 0.000 description 2
- 239000011575 calcium Substances 0.000 description 2
- ZOMBKNNSYQHRCA-UHFFFAOYSA-J calcium sulfate hemihydrate Chemical compound O.[Ca+2].[Ca+2].[O-]S([O-])(=O)=O.[O-]S([O-])(=O)=O ZOMBKNNSYQHRCA-UHFFFAOYSA-J 0.000 description 2
- 210000004027 cell Anatomy 0.000 description 2
- 239000012153 distilled water Substances 0.000 description 2
- 239000007943 implant Substances 0.000 description 2
- 230000002757 inflammatory effect Effects 0.000 description 2
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- 239000002002 slurry Substances 0.000 description 2
- 239000000661 sodium alginate Substances 0.000 description 2
- 235000010413 sodium alginate Nutrition 0.000 description 2
- 229940005550 sodium alginate Drugs 0.000 description 2
- 239000002904 solvent Substances 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- 230000017423 tissue regeneration Effects 0.000 description 2
- 230000001131 transforming effect Effects 0.000 description 2
- MSWZFWKMSRAUBD-IVMDWMLBSA-N 2-amino-2-deoxy-D-glucopyranose Chemical compound N[C@H]1C(O)O[C@H](CO)[C@@H](O)[C@@H]1O MSWZFWKMSRAUBD-IVMDWMLBSA-N 0.000 description 1
- SQDAZGGFXASXDW-UHFFFAOYSA-N 5-bromo-2-(trifluoromethoxy)pyridine Chemical compound FC(F)(F)OC1=CC=C(Br)C=N1 SQDAZGGFXASXDW-UHFFFAOYSA-N 0.000 description 1
- 235000001674 Agaricus brunnescens Nutrition 0.000 description 1
- 241000239290 Araneae Species 0.000 description 1
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 1
- 229920000018 Callose Polymers 0.000 description 1
- 229920002134 Carboxymethyl cellulose Polymers 0.000 description 1
- 229920001287 Chondroitin sulfate Polymers 0.000 description 1
- 241000238424 Crustacea Species 0.000 description 1
- 241000195493 Cryptophyta Species 0.000 description 1
- 241000238557 Decapoda Species 0.000 description 1
- 241000371997 Eriocheir sinensis Species 0.000 description 1
- 108010068370 Glutens Proteins 0.000 description 1
- OVRNDRQMDRJTHS-UHFFFAOYSA-N N-acelyl-D-glucosamine Natural products CC(=O)NC1C(O)OC(CO)C(O)C1O OVRNDRQMDRJTHS-UHFFFAOYSA-N 0.000 description 1
- OVRNDRQMDRJTHS-FMDGEEDCSA-N N-acetyl-beta-D-glucosamine Chemical group CC(=O)N[C@H]1[C@H](O)O[C@H](CO)[C@@H](O)[C@@H]1O OVRNDRQMDRJTHS-FMDGEEDCSA-N 0.000 description 1
- MBLBDJOUHNCFQT-LXGUWJNJSA-N N-acetylglucosamine Natural products CC(=O)N[C@@H](C=O)[C@@H](O)[C@H](O)[C@H](O)CO MBLBDJOUHNCFQT-LXGUWJNJSA-N 0.000 description 1
- 206010028980 Neoplasm Diseases 0.000 description 1
- 241001597008 Nomeidae Species 0.000 description 1
- 208000007536 Thrombosis Diseases 0.000 description 1
- BUKPYVZUSQQGJS-UHFFFAOYSA-L [Ca+2].O.[PH2](=O)[O-].[PH2](=O)[O-] Chemical compound [Ca+2].O.[PH2](=O)[O-].[PH2](=O)[O-] BUKPYVZUSQQGJS-UHFFFAOYSA-L 0.000 description 1
- 238000010521 absorption reaction Methods 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 239000003513 alkali Substances 0.000 description 1
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 1
- 229940127219 anticoagulant drug Drugs 0.000 description 1
- 230000010100 anticoagulation Effects 0.000 description 1
- MSWZFWKMSRAUBD-UHFFFAOYSA-N beta-D-galactosamine Natural products NC1C(O)OC(CO)C(O)C1O MSWZFWKMSRAUBD-UHFFFAOYSA-N 0.000 description 1
- 239000003462 bioceramic Substances 0.000 description 1
- 230000008512 biological response Effects 0.000 description 1
- 210000004369 blood Anatomy 0.000 description 1
- 239000008280 blood Substances 0.000 description 1
- 210000001124 body fluid Anatomy 0.000 description 1
- 239000010839 body fluid Substances 0.000 description 1
- 210000001185 bone marrow Anatomy 0.000 description 1
- 230000002308 calcification Effects 0.000 description 1
- 229910052791 calcium Inorganic materials 0.000 description 1
- AXCZMVOFGPJBDE-UHFFFAOYSA-L calcium dihydroxide Chemical compound [OH-].[OH-].[Ca+2] AXCZMVOFGPJBDE-UHFFFAOYSA-L 0.000 description 1
- XAAHAAMILDNBPS-UHFFFAOYSA-L calcium hydrogenphosphate dihydrate Chemical compound O.O.[Ca+2].OP([O-])([O-])=O XAAHAAMILDNBPS-UHFFFAOYSA-L 0.000 description 1
- 239000000920 calcium hydroxide Substances 0.000 description 1
- 229910001861 calcium hydroxide Inorganic materials 0.000 description 1
- BRPQOXSCLDDYGP-UHFFFAOYSA-N calcium oxide Chemical compound [O-2].[Ca+2] BRPQOXSCLDDYGP-UHFFFAOYSA-N 0.000 description 1
- 239000000292 calcium oxide Substances 0.000 description 1
- ODINCKMPIJJUCX-UHFFFAOYSA-N calcium oxide Inorganic materials [Ca]=O ODINCKMPIJJUCX-UHFFFAOYSA-N 0.000 description 1
- 201000011510 cancer Diseases 0.000 description 1
- 150000001720 carbohydrates Chemical class 0.000 description 1
- 239000001768 carboxy methyl cellulose Substances 0.000 description 1
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- 210000002421 cell wall Anatomy 0.000 description 1
- 238000012512 characterization method Methods 0.000 description 1
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- 229940059329 chondroitin sulfate Drugs 0.000 description 1
- 239000002131 composite material Substances 0.000 description 1
- 238000006731 degradation reaction Methods 0.000 description 1
- 238000011161 development Methods 0.000 description 1
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- 210000003194 forelimb Anatomy 0.000 description 1
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- 229960002442 glucosamine Drugs 0.000 description 1
- 230000036571 hydration Effects 0.000 description 1
- 238000006703 hydration reaction Methods 0.000 description 1
- 229910052739 hydrogen Inorganic materials 0.000 description 1
- 239000001257 hydrogen Substances 0.000 description 1
- 239000001866 hydroxypropyl methyl cellulose Substances 0.000 description 1
- 235000010979 hydroxypropyl methyl cellulose Nutrition 0.000 description 1
- 229920003088 hydroxypropyl methyl cellulose Polymers 0.000 description 1
- UFVKGYZPFZQRLF-UHFFFAOYSA-N hydroxypropyl methyl cellulose Chemical compound OC1C(O)C(OC)OC(CO)C1OC1C(O)C(O)C(OC2C(C(O)C(OC3C(C(O)C(O)C(CO)O3)O)C(CO)O2)O)C(CO)O1 UFVKGYZPFZQRLF-UHFFFAOYSA-N 0.000 description 1
- 230000005847 immunogenicity Effects 0.000 description 1
- 238000002513 implantation Methods 0.000 description 1
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- 229920000609 methyl cellulose Polymers 0.000 description 1
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- 229950006780 n-acetylglucosamine Drugs 0.000 description 1
- 231100000252 nontoxic Toxicity 0.000 description 1
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- LFULEKSKNZEWOE-UHFFFAOYSA-N propanil Chemical compound CCC(=O)NC1=CC=C(Cl)C(Cl)=C1 LFULEKSKNZEWOE-UHFFFAOYSA-N 0.000 description 1
- 210000003689 pubic bone Anatomy 0.000 description 1
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- 235000015170 shellfish Nutrition 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 239000001488 sodium phosphate Substances 0.000 description 1
- 229910000162 sodium phosphate Inorganic materials 0.000 description 1
- 239000012064 sodium phosphate buffer Substances 0.000 description 1
- 229940074404 sodium succinate Drugs 0.000 description 1
- ZDQYSKICYIVCPN-UHFFFAOYSA-L sodium succinate (anhydrous) Chemical compound [Na+].[Na+].[O-]C(=O)CCC([O-])=O ZDQYSKICYIVCPN-UHFFFAOYSA-L 0.000 description 1
- 208000011580 syndromic disease Diseases 0.000 description 1
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- RYFMWSXOAZQYPI-UHFFFAOYSA-K trisodium phosphate Chemical compound [Na+].[Na+].[Na+].[O-]P([O-])([O-])=O RYFMWSXOAZQYPI-UHFFFAOYSA-K 0.000 description 1
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Landscapes
- Materials For Medical Uses (AREA)
- Dental Preparations (AREA)
Abstract
The invention discloses a bone repairing material, which is high in mechanical intensity. The adopted technical project: chitin ramification 0.01-10% in solution form added in or compounded in synthetical high-molecular materials such as bone cement system, polylactic acid, etc. The chitin ramification can be phosphatized chitin, phosphatized chitosan, carboxyl-butyl chitosan and carboxylic vitriolic esterified chitosan. The bone repairing material is a reliable endo-degradable tissue repairing and curing material, having wide application value in repairing tissues (such as bone, cartilage, teeth).
Description
Technical field
The present invention relates to tissue renovation material, particularly relate to a kind of bone renovating material.
Background technology
Chitin (Chitin) has another name called chitin, chitin, chitin, glutelin etc., be a kind of keep and protect water insoluble, the alkali of crustacean and microorganism body and linear aminopolysaccharide of conventional solvent, extensively be present in (Chen Tian in the wing of the sufficient animal class of joint (Araneae, shell-fish) or the cell wall of shell and mushroom and algae, Yan Jun, Xu Rongnan, Xia Yan. biomedical engineering's magazine, 1989; 6 (1): 60.), nearly 1,000,000,000 tons more than of annual biosynthesis only just has 10～30% content in the carapace garbage after processing of aquatic products such as Eriocheir sinensis, shrimp.It is a kind of natural resources that has potential value, waits to develop.Solubility in acid chitosan (Chitosan) is the deacetylated compound of chitin, the derivant that belongs to chitin, molecular weight is 12～590,000, chemistry by name poly-(1,4)-2-amino-2-deoxidation-callose, have tangible alkalescence, excellent biological compatibility and biodegradability, catabolite is N-acetylglucosamine and the glucosamine nontoxic to human body, the intermediate product that produces in the degradation process does not accumulate in vivo, no immunogenicity (Jiang Xuesong, Wang Bosheng etc. biomedical engineering's magazine, 1996; 13 (4): 353.).In recent years, along with going deep into extensive of research, the application of chitin derivativ has related to many departments or fields such as weaving, printing and dyeing, papermaking, medical treatment and water treatment.Especially as the biomaterial with special performance, more and more attract much attention, some project has had productive value and Practical significance.
The reparation of tissue repair, especially large segmental bone defect is the surgical thorny problem of puzzlement always.In the decades in past, although prepared many kinds of bone alternate materials, 70% bone alternate material still uses from body bone or allograph bone clinically, makes patient face high operation syndrome and infection rate.Because people also lack confidence to existing bone renovating material, relate in particular to problem (the Langstaff S of interior safety of secular body and effect, Sayer M, Smith TJN, Pugh SM.Resorbable bioceramics based on stabilized calciumphosphates.Part II:evalu tion of biological response.Biomaterials, 2001; 22:135.), the use of synthetic material is restricted.
Calcium phosphate bone cement has the biomaterial of development potentiality as a class because its high bone conductibility, easily with synosteosis, plastotype (or injection) reaches characteristics such as degraded gradually easily, more and more draw attention.At present, the bone cement of reporting in the domestic and foreign literature more than 15 kinds, most of with hydroxyapatite (HA) as its unique or main end-product.Tetracalcium phosphate and anhydrous (or two hydrations) calcium hydrogen phosphate, zinc oxide and phosphoric acid, single hypophosphite monohydrate calcium dihydrogen, alpha-calcium phosphate and calcium carbonate, beta-calcium phosphate, dalcium biphosphate and calcium sulfate hemihydrate etc. are bone cement system commonly used.Hydroxyapatite is the main component of inorganic salt in sclerous tissues's (as bone, tooth).Compare with natural bone, organic shortage is defeated and dispersed (Hong YC when causing bone cement to contact with blood in early days, Wang JT, Brown WE.Chow LC.Theperiapical tissue react ions to a calcium phosphate cement in the teeth ofmonkeys.J Biomed Mater Res, 1991; 25:485), the easily tired main cause in back that implants.
In order to improve the performance of bone cement, multiple organic additive is referred in the bone cement.As sodium alginate (Ishikawa K, Miyamoto Y, Kon M, Nagayama M, Asaoka K.Non-decay typefast-setting calcium phosphate cement:composite with sodium alginate.Biomaterials, 1995; 16:527.), (hydrogen) prolyl methylcellulose and carboxymethyl cellulose (CherngA, Takagi S, Chow LC.Effects of hydroxypropyl methylcellulose and othergelling agents on the handling properties of calcium phosphate cement.J BiomedMater Res, 1997; 35:273.) once be used to strengthen the bonding force of tetracalcium phosphate (TTCP) bone cement, but the firm time of bone cement may be extended, or mechanical strength descends, or Organic substance is difficult to be degraded in vivo, and nearly all Organic substance all can have side effects to the performance of bone cement.
Summary of the invention
The purpose of this invention is to provide the higher bone renovating material of a kind of mechanical strength.
For achieving the above object, the present invention by the following technical solutions: a kind of bone renovating material is chitin derivativ or the compound bone cement system of 0.01-10% chitin derivativ of the 0.01-10% of solution form.
The preferred addition of described chitin derivativ is 1-5%.
The solvent of the bone renovating material of the present invention of solution form can be distilled water, normal saline etc., also chitin derivativ can be mixed with materials such as calcium phosphate or synthesized polymer materials such as bone cement system, polylactic acid, make starchiness thing or solid, solution or starchiness thing can be injected directly into the bone defect, and solid, shaped can implant by operation.
Described chitin derivativ can be the phosphorylation chitin, and the hydroxyl substitution value of phosphorylation chitin is 0.05～0.99, and molecular weight is 5000～10000 dalton; Also can be phosphonized chitosan, the deacetylation of phosphonized chitosan be 5～95%, and the hydroxyl substitution value is 0.02～0.95, and molecular weight is 5000～10000 dalton; Can also be carboxylic butyl chitosan, the deacetylation of carboxylic butyl chitosan be 10～90%, and the hydroxyl substitution value is 0.05～0.95, and molecular weight is 2 * 10
4～6 * 10
6Dalton; For osteoma and leukaemic, can be again carboxylated Sulfation chitosan, the deacetylation of carboxylated Sulfation chitosan is 15～95%, and the hydroxyl substitution value is 0.01～0.75, and molecular weight is 5000～10000 dalton.
Phosphorylation chitin of the present invention, phosphonized chitosan can be according to document Nishi N, Ebina A, NishimuraS, Tsutsumi A, Hasegawa O, Tokura S.Highly phosphorylated derivatives ofchitin, partially deacetylated chitin and chitosan as new functional polymers:preparation and characterization.Int J Biol Macromol 1986; The described method preparation of 8:311-317.Carboxylic butyl chitosan can be by document MuzzarelliR, Weckx M, Filippini O, Lough C.Characteristic Properties of N-Carboxybutyl Chitosan.Carbohydrate Polymers1989; The described method preparation of II:307-320.Carboxylated Sulfation chitosan can be by document Horton D, JustEK.Preparation from chitin of (1 → 4)-2-amino-2-deoxy-β-D-glucopyranuronanand its 2-sulfoamino analog having blood-anticoagulant properties.CarbohydrRes 1973; The described method preparation of 29:173-179.
The present invention utilizes the chitin derivativ aqueous solution or prepares bone renovating material with the complex of calcium phosphate etc.Can avoid operating misery by injecting the purpose that promptly reach treatment for sufferers of osteoporosis face.For calcium phosphate bone cement, can make its mechanical strength on average improve 5-100%.Cell experiment and zoopery all show, chitin derivativ has excellent biological compatibility and induced osteogenesis activity, bone renovating material of the present invention is a kind of tissue repair and treatment material of reliable degradable in vivo, is with a wide range of applications in tissue (as bone, cartilage, tooth) is repaired.
The present invention will be further described below in conjunction with specific embodiment.
The specific embodiment
Embodiment 1:
With equimolar tetracalcium phosphate (TTCP) and calcium hydrogen phosphate (DCPD or DCPA) fine powder mix homogeneously, add and contain 2.0% phosphonized chitosan (deacetylation: 60%; Substitution value: 0.50; Molecular weight: 5 * 10
3) the sodium phosphate buffer of 0.2 M, solid-to-liquid ratio (P/L) is 4: 1.Slurry can be injected directly into the bone defect or solidify 40 minutes to such an extent that comprcssive strength is the bone cement of 150MPa.This kind bone cement can be used for bone, reparation that tooth is damaged, has in vivo that antithrombotic forms, the ability of anti-inflammatory response.Material is converted into area of new bone after being soaked into by body fluid, does not have fibers encapsulation between material and new bone.
Get 15 of adult rabbits, be divided into 3 groups at random, 5 every group, be respectively experimental group, positive controls and negative control group.Each makes a call to the hole of 3 millimeters of diameters, 3 millimeters of the degree of depth in the same area of every rabbit hind leg pubis with the surgical method of routine, carry out the routine wrapping after being packed into the pulpous state bone renovating material of this embodiment of the invention in the hole of experimental group, positive controls is packed into dalcium biphosphate, calcium oxide bone cement system, carry out the routine wrapping, negative control group does not process promptly carries out the routine wrapping.Observe the osteogenesis situation of respectively organizing laboratory animal, the result shows, the site of injury of experimental group animal is from beginning to have the reticulated bone that is induced to form in the 4th week, recovery from illness in 6 months, it is smoothly neat to repair the position, do not have fibers encapsulation between material and the new bone, bone and soft tissue on every side do not have inflammatory phenomena to take place during the bone formation; The site of injury of positive control treated animal was fully recovered from the bone that begins to occur transforming formation the 4th week in 3 months, and reparation position and edge have more concavo-convex, and inflammatory reaction has appearred in the soft tissue around bone reaches during the bone formation; The hole place of negative control treated animal does not have bone formation, and inflammatory reaction is arranged.From The above results as can be seen, bone renovating material of the present invention is being induced the osteoplastic while, also has the effect of anti-inflammatory response.
Embodiment 2:
(α-TCP), dalcium biphosphate (MCPM) and calcium carbonate (Ca2CO3) fine powder are that the mixed of 71: 5.8: 23.5 (or 12: 1: 4 mol ratios) is even by ratio of weight and the number of copies with alpha-calcium phosphate.Be that 0.1g/ml, substitution value are 0.25, molecular weight is 4.25 * 10 with concentration again
4Sodium phosphate (the Na of the phosphorylation chitin of Da
3PO
4) solution (2.78mol/1) is by the mixed sample preparation of liquid-solid ratio (l/s) 1: 2 (w/w).Slurry (solid-liquid mixes in back 20 minutes) can be injected directly into the bone defect, is used to not have the reparation at heavy burden position.Solidified 24 hours under 30 ℃, 80% humidity, the mechanical comprcssive strength of the bone cement that makes is 180MPa.Be used for bone, regeneration, reparation that tooth is damaged.
Get 15 of adult rabbits, be divided into 3 groups at random, 5 every group, be respectively experimental group, positive controls and negative control group.Surgical method with routine excises 9 millimeters with the same area of every rabbit forelimb radius, carry out the routine wrapping behind the bone cement of the animal excision place implantation this embodiment of the invention of experimental group, positive controls is implanted calcium phosphate dibasic dihydrate, calcium hydroxide bone cement system, carry out the routine wrapping, negative control group does not process promptly carries out the routine wrapping.Observe the osteogenesis situation of respectively organizing laboratory animal, the result shows, the site of injury of experimental group animal is from beginning to have the reticulated bone that is induced to form in the 4th week, recovery from illness in 6 months, it is smoothly neat to repair the position, does not have fibers encapsulation between material and the new bone, and bone and soft tissue on every side do not have inflammatory phenomena to take place during the bone formation, the new sclerotin ground that forms is pliable and tough, is not prone to the secondary fracture; The site of injury of positive control treated animal begins to occur transforming the bone of formation from the 4th week, recovery from illness in 3 months, reparation position and edge have more concavo-convex, and inflammatory reaction has appearred in the soft tissue around bone reaches during the bone formation, the new sclerotin ground that forms is more crisp, occurs the secondary fracture easily; Excision place of negative control treated animal does not have bone formation, and inflammatory reaction and thrombosis are arranged.From The above results as can be seen, bone renovating material of the present invention not only has the big section osteoplastic effect of inducing, and also has antiinflammatory and antithrombotic effect simultaneously.
Embodiment 3:
With alpha-calcium phosphate (α-TCP), calcium hydrogen phosphate (DCPD) and tetracalcium phosphate [TTCP, Ca
4(PO
4)
2] fine powder is by the percentage by weight mix homogeneously of 75%: 5.0%: 20.0% (w/w).Again with 2% phosphonized chitosan (deacetylation: 70%; Substitution value: 0.30; Molecular weight: 5 * 10
3), the aqueous solution (P/L) of 5% chondroitin sulfate, 10% sodium succinate mixes sample preparation by solid-to-liquid ratio 1: 3 (w/w).The bone cement that makes is put into simulated body fluid (SBF) soaked 7 days, getting mechanical comprcssive strength is the bone cement of 130Mpa.Have when being used for the damaged reparation of big section bone, tooth that antithrombotic forms, the ability of anti-inflammatory response.Directly combine middle no fibers encapsulation between material and the area of new bone.
Embodiment 4:
With beta-calcium phosphate, dalcium biphosphate, calcium sulfate hemihydrate fine powder and contain 1% carboxylic butyl chitosan (deacetylation is 80%, substitution value: 0.8; Molecular weight is 5 * 10
5Da) distilled water was by weight 42: 13: 10: 35 mix homogeneously are injected directly into no heavy burden bone defect, or solidify 24h under 38 ℃, 100% humidity.Confirm that through animal and human experimentation the gained solidfied material is used for bone, reparation that tooth is damaged, no fatigue phenomenon, and with anticoagulation, anti-inflammatory effect.
Embodiment 5:
Carboxylated Sulfation chitosan (deacetylation: 75% with 2%; Substitution value: 0.6; Molecular weight: 6 * 10
3Da) aqueous solution is expelled in the bone marrow of canceration.Dosage is 200mg/kg/day, kill cancer cell is arranged, suppress the effect that leukocyte is bred.
Embodiment 6:
Phosphonized chitosan with 2.5% (deacetylation: 850%; Substitution value: 0.47; Molecular weight: 4.8 * 10
3) be dissolved into in the NaCl solution, be subcutaneously injected into then in the muscle of sufferers of osteoporosis face.Dosage is 500mg/kg/day, and the result shows, can promote absorption, the sclerotin calcification of calcium.
Claims (10)
1, a kind of bone renovating material is chitin derivativ or the compound bone cement system of 0.01-10% chitin derivativ of the 0.01-10% of solution form.
2, bone renovating material according to claim 1 is characterized in that: the addition of described chitin derivativ is 1-5%.
3, bone renovating material according to claim 1 and 2 is characterized in that: described chitin derivativ is the phosphorylation chitin.
4, bone renovating material according to claim 3 is characterized in that: the substitution value of described phosphorylation chitin is 0.05-0.95, and molecular weight is 5000-10000 dalton.
5, bone renovating material according to claim 1 and 2 is characterized in that: described chitin derivativ is a phosphonized chitosan.
6, bone renovating material according to claim 5 is characterized in that: the deacetylation of described phosphonized chitosan is 5-95%, and the hydroxyl substitution value is 0.02-0.95, and molecular weight is 5000-10000 dalton.
7, bone renovating material according to claim 1 and 2 is characterized in that: described chitin derivativ is a carboxylic butyl chitosan.
8, bone renovating material according to claim 7 is characterized in that: the deacetylation of described carboxylic butyl chitosan is 10-90%, and the hydroxyl substitution value is 0.05-0.95, and molecular weight is 2 * 10
4-6 * 10
6Dalton.
9, bone renovating material according to claim 1 and 2 is characterized in that: described chitin derivativ is carboxylated Sulfation chitosan.
10, bone renovating material according to claim 7 is characterized in that: the deacetylation of described carboxylated Sulfation chitosan is 15-95%, and the hydroxyl substitution value is 5000-10000 dalton for the 0.01-0.75 molecular weight.
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| CN 02125614 CN1230181C (en) | 2002-07-24 | 2002-07-24 | Bone repairing material |
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| CN 02125614 CN1230181C (en) | 2002-07-24 | 2002-07-24 | Bone repairing material |
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| CN1230181C CN1230181C (en) | 2005-12-07 |
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Cited By (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102390941A (en) * | 2011-08-10 | 2012-03-28 | 徐华梓 | Medical alpha-hemihydrate calcium sulfate artificial bone repairing material and preparation method thereof |
| CN101687059B (en) * | 2007-02-14 | 2013-03-27 | 格拉夫蒂斯公司 | Injectable calcium-phosphate cement releasing a bone resorption inhibitor |
| CN103880981A (en) * | 2012-12-21 | 2014-06-25 | 中国科学院大连化学物理研究所 | Method for synthesizing phosphorylated chitin by taking methanesulfonic acid as solvent |
| CN104231112A (en) * | 2014-04-29 | 2014-12-24 | 深圳大学 | Synthesis method of 6-O-carboxymethyl chitosan sulfuric sulfation product |
| JP2017036369A (en) * | 2015-08-07 | 2017-02-16 | 株式会社イノアック技術研究所 | Method for producing soluble phosphorylated chitin or soluble phosphorylated collagen, method for producing composite of phosphorylated chitin or phosphorylated collagen and titanium, method for producing polyurethane foam, composite, method for producing phosphorylated collagen, and method for producing composite of phosphorylated collagen and titanium |
| CN107473697A (en) * | 2017-07-25 | 2017-12-15 | 成都理工大学 | Earthen ruins Dam Foundation Strengthened in Situ repair materials, its preparation method and application |
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2002
- 2002-07-24 CN CN 02125614 patent/CN1230181C/en not_active Expired - Fee Related
Cited By (10)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101687059B (en) * | 2007-02-14 | 2013-03-27 | 格拉夫蒂斯公司 | Injectable calcium-phosphate cement releasing a bone resorption inhibitor |
| CN102390941A (en) * | 2011-08-10 | 2012-03-28 | 徐华梓 | Medical alpha-hemihydrate calcium sulfate artificial bone repairing material and preparation method thereof |
| CN102390941B (en) * | 2011-08-10 | 2013-01-23 | 徐华梓 | Medical alpha-hemihydrate calcium sulfate artificial bone repairing material and preparation method thereof |
| CN103880981A (en) * | 2012-12-21 | 2014-06-25 | 中国科学院大连化学物理研究所 | Method for synthesizing phosphorylated chitin by taking methanesulfonic acid as solvent |
| CN104231112A (en) * | 2014-04-29 | 2014-12-24 | 深圳大学 | Synthesis method of 6-O-carboxymethyl chitosan sulfuric sulfation product |
| CN104231112B (en) * | 2014-04-29 | 2016-03-23 | 深圳大学 | A kind of synthetic method of CARB OXYMETHYL-CHITOSAN sulfation product |
| JP2017036369A (en) * | 2015-08-07 | 2017-02-16 | 株式会社イノアック技術研究所 | Method for producing soluble phosphorylated chitin or soluble phosphorylated collagen, method for producing composite of phosphorylated chitin or phosphorylated collagen and titanium, method for producing polyurethane foam, composite, method for producing phosphorylated collagen, and method for producing composite of phosphorylated collagen and titanium |
| CN107473697A (en) * | 2017-07-25 | 2017-12-15 | 成都理工大学 | Earthen ruins Dam Foundation Strengthened in Situ repair materials, its preparation method and application |
| CN114082000A (en) * | 2021-12-08 | 2022-02-25 | 深圳市儿童医院 | Biodegradable drug-loaded high polymer material stent and preparation method thereof |
| CN114082000B (en) * | 2021-12-08 | 2022-07-29 | 深圳市儿童医院 | Biodegradable drug-loaded high polymer material stent and preparation method thereof |
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